The present invention provides preservation solutions useful for storing organs while awaiting implantation which extend the vitality of the organ and reduce damage to organ cells. The present invention also provides method for preserving organs which extend the maximum life of the organ before and during transplantation.
A great deal of research progress has been made over the years in understanding cellular mechanisms, as well as developing new transplantation techniques, for keeping organs viable not only during storage but also after reperfusion of these organs (e.g., minimization of ischemia/reperfusion injury). As a result, organ transplantation has become an established and effective technique. A significant factor limiting clinical application of organ transplantation is decrease in viability of the organ after removal from the donor.
Generally, the two most frequently used methods for preserving organs after removal from the donor are simple hypothermic storage and continuous pulsatile perfusion. With simple hypothermic storage, the organ is removed from the donor and cooled rapidly. This is usually achieved by a combination of cooling and short periods of perfusion to drop the organ temperature as quickly as possible to a temperature between 0° C. and 4° C., where it may be held for up to about six hours. While cold storage enables organs to be transplanted, the time during which the organ is viable is short. Cold storage decreases the rate at which intracellular enzymes, essential cellular components necessary for organ viability, degrade but does not stop metabolism entirely.
The second method of organ preservation which has undergone extensive investigation, continuous pulsatile perfusion, utilizes the following elements: (1) pulsatile flow, (2) hypothermia, (3) membrane oxygenation, and (4) a perfusate containing both albumin and lipids. Although being more technically complex and costly, continuous pulsatile perfusion provides significantly longer viability of the organ when compared to simple hypothermia.
Preserving organs at between 0° C. and 4° C. can result in damage to the organ during storage and upon reperfusion with a warm reperfusion solution. Injury to the organ occurs through damage to epithelial, endothelial and parenchymal cells. Although some of the solutions of the prior art have been useful to extend the storage time of donor organs and lessen injury to the organ upon reperfusion, cell injury still does occur frequently. It is desirable to extend the viable organ life and improve the quality of the transplanted organ. For example, using preservation solutions of the prior art, kidneys that have been in cold storage beyond 48 hours frequently cannot be used and must be discarded. Extending organ viability allows sufficient time for compatibility testing of the donor and recipient, and increased organ availability. It is also desirable to minimize damage to the organ upon reperfusion. Ischemia-reperfusion injury to transplanted organs preserved in solutions of the prior art commonly results in delayed graft function, and predisposes the graft to acute and chronic rejection.
There remains a need in the art for improved methods and compositions for conservation and preparation of organs and tissues for transplant.